|
【结 构 式】 
|
【分子编号】31144 【品名】N-hydroxy-3,5-dimethyl-4-[3-(3-methyl-5-isoxazolyl)propoxy]benzenecarboximidamide 【CA登记号】 |
【 分 子 式 】C16H21N3O3 【 分 子 量 】303.36116 【元素组成】C 63.35% H 6.98% N 13.85% O 15.82% |
合成路线1
该中间体在本合成路线中的序号：(IX)The condensation of 3,5-dimethylisoxazole (I) with ethylene oxide (II) by means of butyllithium in THF gives 3-(3-methylisoxazol-5-yl)-1-propanol (III), which by reaction with refluxing SOCl2 yields the corresponding propyl chloride (IV). The condensation of (IV) with 4-hydroxy-3,5-dimethylbenzonitrile (V) [obtained by reaction of 4-bromo-2,6-dimethylphenol (VI) with Cu2CN2 in refluxing DMF] by means of K2CO3 and KI in hot N-methylpyrrolidone affords 3,5-dimethyl-4-[3-(3-methylisoxazol-5-yl)propoxy]benzonitrile (VII). The reaction of (VII) with hydroxylamine (VIII) and K2CO3 in refluxing ethanol gives the corresponding benzohydroxamic acid (IX), which is finally cyclized with refluxing trifluoroacetic anhydride and pyridine.
| 【1】 Diana, G.D.; Rudewicz, P.; Pevear, D.C.; et al.; Picornavirus inhibitors: Trifluoromethyl substitution provides a global protective effect against hepatic metabolism. J Med Chem 1995, 38, 1355-71. |
| 【2】 Fromtling, R.A.; Castañer, J.; VP-63843. Drugs Fut 1997, 22, 1, 40. |
| 【3】 Diana, G.D.; Nitz, T.J. (Sanofi-Synthelabo); 1,2,4-Oxadiazolyl-phenoxyalkylisoxazoles and their use as antiviral agents. EP 0566199; JP 1994049066; US 5349068 . |
| 【4】 Diana, G.D.; Nitz, T.J. (Sanofi-Synthelabo); 1,2,4-Oxadiazolyl-phenoxyalkylisoxazoles and their use as antiviral agents. US 5464848 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 31138 | 3,5-dimethylisoxazole | 300-87-8 | C5H7NO | 详情 | 详情 |
| (II) | 10393 | Oxirane; Ethylene oxide | 75-21-8 | C2H4O | 详情 | 详情 |
| (III) | 31139 | 3-(3-methyl-5-isoxazolyl)-1-propanol | C7H11NO2 | 详情 | 详情 | |
| (IV) | 31140 | 5-(3-chloropropyl)-3-methylisoxazole | 130800-76-9 | C7H10ClNO | 详情 | 详情 |
| (V) | 31141 | 4-Hydroxy-3,5-dimethylbenzonitrile; 2,6-Dimethyl-4-hydroxybenzonitrile | 4198-90-7 | C9H9NO | 详情 | 详情 |
| (VI) | 31142 | 4-bromo-2,6-dimethylphenol | 2374-05-2 | C8H9BrO | 详情 | 详情 |
| (VII) | 31143 | 3,5-dimethyl-4-[3-(3-methyl-5-isoxazolyl)propoxy]benzonitrile | C16H18N2O2 | 详情 | 详情 | |
| (IX) | 31144 | N-hydroxy-3,5-dimethyl-4-[3-(3-methyl-5-isoxazolyl)propoxy]benzenecarboximidamide | C16H21N3O3 | 详情 | 详情 |